Plasma cell sarcoma complicating a case of multiple myeloma.

Several authors have drawn attention to malignant transformation as a terminal feature of multiple myelo-matosis (Editorial, B.M.J., 1971). Both acute leukaemia and plasma cell sarcoma have been described, ar)d it has been suggested that the malignant change ^ay be related to treatment. We describe a further case of multiple myelomatosis terrr|inating in a plasma cell sarcoma in which the striking features were massive involvement of the Pleura, the cytological examination of pleural aspirate l? make the diagnosis and the rapid onset of the Second malignancy.

'NTRODUCTION Several authors have drawn attention to malignant transformation as a terminal feature of multiple myelomatosis (Editorial, B.M.J., 1971). Both acute leukaemia and plasma cell sarcoma have been described, ar)d it has been suggested that the malignant change ^ay be related to treatment.
We describe a further case of multiple myelomatosis terrr|inating in a plasma cell sarcoma in which the striking features were massive involvement of the Pleura, the cytological examination of pleural aspirate l? make the diagnosis and the rapid onset of the Second malignancy.
^ase Report ^ A 52-year-old plant operator presented in September ^2 vyjth a tw0 month history of progressive shortness of breath and palpitations. He had been previously apart from troublesome nose bleeds over the past ?ur years. Examination revealed pallor, bleeding from "ttle's area of the nostrils and scattered retinal aernorrhages. lrivestigations Haemoglobin 8.0 g/dl (normal indices), normal plasma viscosity 3.64 cp (normal 1.50-1.72 cp), total protein 138 g/l (albumen 18 g/I discrete band |n 9amma region). IgG 98 g/l (normal 8.4-17.0 Following this he remained well for fourteen months with intermittent melphalan (10 mg.) and prednisolone (40 mg.) for 7 days every six weeks. In February 1974 he was readmitted with a tender, swollen left calf. Chest clear, chest X-ray and ECG normal. He was anticoagulated for a presumed deep venous thrombosis. He attended for follow-up one month later, and was perfectly well with normal physical examination and a normal chest X-ray. Haemoglobin 12.1 g/dl, IgG 16, IgA 1.3, IgM 1.0, plasma viscosity 1.52.
Creatinine clearance 100 ml. per minute. Bence Jones proteinuria not detected. The chest was aspirated, yielding 500 ml. clear fluid. On cytocentrifugation, large numbers of abnormal plasma cells were seen. The bone marrow was replaced by large numbers of primitive cells. Warfarin was stopped and vitamin K, blood and platelet transfusions given. Chemotherapy with the TRAP regime started. (Thioguanine 100 mg. and prednisolone 30 mg. per square metre orally for five days, daunorubicin 40 mg. per square metre intravenously on the first day and cytosine arabinoside 100 mg. per square metre intravenously daily for five days.) Repeated chest aspirations were required and a total of five litres of fluid were removed. He died before the first course of chemotherapy was completed.

Comment
The striking features in this case were the findings in the bone marrow and pleural aspirate, when the patient suddenly presented with severe shortness of breath in April 1974. The marrow was heavily infiltrated with bizarre mononuclear cells which constituted 63% of the total nucleated cells. These cells were large and appeared as plasmacytoid cells showing abnormal mitoses with active and abundant cytoplasm with occasional vacuolation. Erythropoiesis and granulopoiesis were markedly depressed. Megakaryocytes were scenty. Cytochemical study revealed pyroninophilic cells which were PAS negative. The reticulin pattern was slightly increased in the histological section of the bone marrow. A cytocentrifuge preparation of the pleural aspirate showed large numbers of strikingly similar cells (Figure 1).
Post Mortem (Dr. C. R. Tribe) The left pleural cavity was completely filled with heavily bloodstained fluid ?nd there were numerous soft, pink, dome-shaped tumour nodules varying in size up to 5 cm. in diameter studded over the visceral and parietal pleura. Similar tumour nodules were present in the anterior mediastinum and the mediastinal lymph nodes were involved.
Histological sections of a pleural tumour show large numbers of plasma cells, varying in size and shape with many multi-nucleated and giant cell forms. The liver, spleen and vertebral bone marrow showed diffuse infiltration with similar cells.

Discussion
The termination of multiple myeloma in a widely disseminated myelogenous leukaemia has been reported by several investigators. Nordenson (1966) in a review of 310 cases of multiple myeloma found two cases which developed into acute myelomonocyte leukaemia and a further five cases terminating in acute lymphoblastic leukaemia. Andersen and Vidabaek (1970) reported four out of nineteen cases of myeloma in which myelomonocy.tic leukaemia developed during the course of treatment with melphalan and/or cyclophosphamide. Kyle and iPierre (1970) reported four oases of myeloma terminating in myeloblastic leukaemia. These authors raised the possibility that cytotoxic drugs might be leukaemogenic. In all these cases they showed at the terminal stage a diffuse leukaemic infiltration of the bone marrow and the peripheral blood, despite return of immunoglobulin levels to normal.

Holt
and Robb-Smith (1973) described three patients with multiple myeloma who developed a plasma cell sarcoma during the course of treatment and suggested that the malignant transformation was a result of therapy.
In the case presented here, the sudden development of severe shortness of breath was a result of the massive pleural effusion due to infiltration of the pleura by tumour. The peripheral blood showed 12% of atypical mononuclear cells which closely resembled those found in the bone marrow and pleural fluid. It should be recognised that a significant number of cases of myelomatosis will terminate in plasma cell sarcoma. In view of the possibility that this change may be related to therapy, it is important to approach with caution the question of long term treatment with cytotoxic agents in patients with symptomless myelomatosis.